Reaction Steps
A sealed tube was charged with 6-chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridine-2-yl)imidazo[1,2-b]pyridazin-8-amine 105a (200 mg, 0.5 mmol), 114e (200 mg, 1.0 eq., 0.5 mmol), Pd2(dba)3 (46 mg, 0.1 eq., 0.05 mmol), PCy3 (40 mg, 0.2 eq., 0.1 mmol), cesium carbonate (325 mg, 2 eq., 1.0 mmol), and dioxane (10 mL). After three cycles of vacuum/argon flash, the mixture was heated at 130° C. for 14 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (40:1) and further purified with reverse-phase prep-HPLC to afford 114 (13 mg, 4%). LCMS: [M+H]+ 647. 1H NMR (500 MHz, DMSO) δ 9.96 (s, 1H), 8.56 (d, J=5.0, 1H), 8.24 (s, 1H), 8.18 (s, 1H), 7.99 (d, J=2.5, 1H), 7.68 (s, 1H), 7.45-7.50 (m, 3H), 6.58 (s, 1H), 4.72 (t, J=5.0, 1H), 4.55-4.59 (m, 3H), 4.45-4.47 (m, 2H), 4.37-4.40 (m, 1H), 4.19-4.29 (m, 2H), 4.08-4.10 (m, 1H), 3.91-3.94 (m, 1H), 3.42-3.45 (m, 1H), 3.14-3.16 (m, 4H), 2.52-2.63 (m, 2H), 2.46-2.47 (m, 2H), 2.36-2.40 (m, 4H), 1.76-1.78 (m, 2H), 1.66-1.70 (m, 2H)
